Baumann, Lisa

Braunbeck, Thomas

G\uf6lz, Lisa

Knapen, Dries

Pannetier, Pauline

Vergauwen, Lucia

Abstract: Thyroid hormones (THs) are involved in the regulation of many important physiological and developmental processes,including vertebrate eye development. Thyroid hormone system\u2013disrupting chemicals (THSDCs) may have severe con-sequences, because proper functioning of the visual system is a key factor for survival in wildlife. However, the sequence ofevents leading from TH system disruption (THSD) to altered eye development infish has not yet been fully described. Thedevelopment of this adverse outcome pathway (AOP) was based on an intensive literature review of studies that focused onTHSD and impacts on eye development, mainly infish. In total, approximately 120 studies (up to the end of 2021) were usedin the development of this AOP linking inhibition of the key enzyme for TH synthesis, thyroperoxidase (TPO), to effects onretinal layer structure and visual function infish (AOP\u2010Wiki, AOP 363). In a weight\u2010of\u2010evidence evaluation, the confidencelevels were overall moderate, with ample studies showing the link between reduced TH levels and altered retinal layerstructure. However, some uncertainties about the underlying mechanism(s) remain. Although the current weight\u2010of\u2010evidenceevaluation is based onfish, the AOP is plausibly applicable to other vertebrate classes. Through the re\u2010use of several buildingblocks, this AOP is connected to the AOPs leading from TPO and deiodinase inhibition to impaired swim bladder inflation infish (AOPs 155\u2013159), together forming an AOP network describing THSD infish. This AOP network addresses the lack ofthyroid\u2010related endpoints in existingfish test guidelines for the evaluation of THSDCs

AOP report : thyroperoxidase inhibition leading to altered visual function in fish via altered retinal layer structure

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